The flexible regulation of emotional processes is a hallmark of normal adaptive behavior. To wit, the same stimulus or action can elicit a positive emotional response in one situation, but a negative one in another situation. In general, stimuli or actions can acquire affective meaning through experience. Subjects learn that previously neutral stimuli or actions predict rewarding or aversive events. Thus the motivational significance, or value, of stimuli can be changed by virtue of this experience. Here, value can have either positive or negative valence. Emotional responses to these stimuli may be based in large part on the representation of value. This grant explores the mechanisms by which the brain adjusts representations of the value of learned stimuli. Brain structures likely to participae in implementing these processes include the amygdala, long recognized as a critical structure in coordinating emotional responses, and the prefrontal cortex, which contains two brain areas densely interconnected with the amygdala: the anterior cingulate and orbitofrontal cortices. These prefrontal areas are thought to confer the type of flexible regulation required for rapid emotional adjustments. In this grant, we will study two different ways in which the value of stimuli and/or actions may be adjusted. In Aim 1, we will study the role of the amygdala and anterior cingulate cortex in a reversal learning procedure, whereby the previously learned associations of two stimuli reverse (or switch). We will characterize the relationship between processing in the amygdala and ACC during this task, building on our prior work studying the amygdala's relationship with OFC. In Aim 2, we will use two different tasks to study how subjects can adjust their representation of the value of a stimulus by knowing how to apply a rule. In one task, no operant actions are required of the experimental subjects, but reinforcement delivery does follow rules. In the second task, subjects must perform the correct operant action according to a rule in order to obtain reinforcement. The second task was designed to elucidate the differential role of the anterior cingulate cortex, as compared to the orbitofrontal cortex and amygdala, as the anterior cingulate has been proposed to play a prominent role in action valuation, error monitoring, and subsequent adjustments of behavior. This work has direct relevance to understanding the neural circuitry that becomes dysfunctional in many psychiatric disorders, such as mood and anxiety disorders, as well as schizophrenia. In those disorders, dysfunction in amygdala- prefrontal circuitry likely impairs the type of emotional flexibility required for normal mental health.